Diabetes Care Volume 39, Supplement 1, January 2016 S13

2. Classication and Diagnosis of American Diabetes Association

Diabetes
Diabetes Care 2016;39(Suppl. 1):S13S22 | DOI: 10.2337/dc16-S005

CLASSIFICATION
Diabetes can be classied into the following general categories:

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin

2. CLASSIFICATION AND DIAGNOSIS OF DIABETES

deciency)
2. Type 2 diabetes (due to a progressive loss of insulin secretion on the background
of insulin resistance)
3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third
trimester of pregnancy that is not clearly overt diabetes)
4. Specic types of diabetes due to other causes, e.g., monogenic diabetes syn-
dromes (such as neonatal diabetes and maturity-onset diabetes of the young
[MODY]), diseases of the exocrine pancreas (such as cystic brosis), and drug- or
chemical-induced diabetes (such as with glucocorticoid use, in the treatment of
HIV/AIDS or after organ transplantation)

This section reviews most common forms of diabetes but is not comprehensive. For
additional information, see the American Diabetes Association (ADA) position state-
ment Diagnosis and Classication of Diabetes Mellitus (1).
Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinical
presentation and disease progression may vary considerably. Classication is im-
portant for determining therapy, but some individuals cannot be clearly classied as
having type 1 or type 2 diabetes at the time of diagnosis. The traditional paradigms
of type 2 diabetes occurring only in adults and type 1 diabetes only in children are no
longer accurate, as both diseases occur in both cohorts. Occasionally, patients with
type 2 diabetes may present with diabetic ketoacidosis (DKA). Children with type 1
diabetes typically present with the hallmark symptoms of polyuria/polydipsia and
approximately one-third with DKA (2). The onset of type 1 diabetes may be more
variable in adults, and they may not present with the classic symptoms seen in
children. Although difculties in distinguishing diabetes type may occur in all age-
groups at onset, the true diagnosis becomes more obvious over time.
DIAGNOSTIC TESTS FOR DIABETES
Diabetes may be diagnosed based on the plasma glucose criteria, either the fasting
plasma glucose (FPG) or the 2-h plasma glucose (2-h PG) value after a 75-g oral
glucose tolerance test (OGTT) or the A1C criteria (1,3) (Table 2.1).
The same tests are used to screen for and diagnose diabetes and to detect individ-
uals with prediabetes. Diabetes may be identied anywhere along the spectrum of
clinical scenarios: in seemingly low-risk individuals who happen to have glucose testing,
in individuals tested based on diabetes risk assessment, and in symptomatic patients.
Fasting and 2-Hour Plasma Glucose
Suggested citation: American Diabetes Associa-
The FPG and 2-h PG may be used to diagnose diabetes (Table 2.1). The concordance
tion. Classication and diagnosis of diabetes.
between the FPG and 2-h PG tests is imperfect, as is the concordance between A1C Sec. 2. In Standards of Medical Care in
and either glucose-based test. Numerous studies have conrmed that, compared Diabetesd2016. Diabetes Care 2016;39(Suppl. 1):
with FPG cut points and A1C, the 2-h PG value diagnoses more people with diabetes. S13S22
2016 by the American Diabetes Association.
A1C Readers may use this article as long as the work
The A1C test should be performed using a method that is certied by the NGSP is properly cited, the use is educational and not
(www.ngsp.org) and standardized or traceable to the Diabetes Control and for prot, and the work is not altered.
S14 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

Table 2.1Criteria for the diagnosis of diabetes the test result that is above the diagnos-
FPG $126 mg/dL (7.0 mmol/L). Fasting is dened as no caloric intake for at least 8 h.*
tic cut point should be repeated. The di-
OR
agnosis is made on the basis of the
conrmed test. For example, if a patient
2-h PG $200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described by
the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in meets the diabetes criterion of the A1C
water.* (two results $6.5% [48 mmol/mol]) but not
OR FPG (,126 mg/dL [7.0 mmol/L]), that
A1C $6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is person should nevertheless be consid-
NGSP certied and standardized to the DCCT assay.* ered to have diabetes.
OR Since all the tests have preanalytic and
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma analytic variability, it is possible that an
glucose $200 mg/dL (11.1 mmol/L). abnormal result (i.e., above the diagnostic
*In the absence of unequivocal hyperglycemia, results should be conrmed by repeat testing.
threshold), when repeated, will produce a
value below the diagnostic cut point. This
scenario is least likely for A1C, more likely
Complications Trial (DCCT) reference as- of fructosamine and glycated albumin and for FPG, and most likely for the 2-h PG,
say. Although point-of-care A1C assays lower levels of 1,5-anhydroglucitol, sug- especially if the glucose samples remain
may be NGSP certied, prociency testing gesting that their glycemic burden (partic- at room temperature and are not centri-
is not mandated for performing the test, ularly postprandially) may be higher (8). fuged promptly. Barring laboratory error,
so use of point-of-care assays for diagnos- Moreover, the association of A1C with such patients will likely have test results
tic purposes is not recommended. risk for complications is similar in African near the margins of the diagnostic thresh-
The A1C has several advantages com- Americans and non-Hispanic whites (9). old. The health care professional should
pared with the FPG and OGTT, including follow the patient closely and repeat the
Hemoglobinopathies/Anemias
greater convenience (fasting not re- test in 36 months.
Interpreting A1C levels in the presence of
quired), greater preanalytical stability, certain hemoglobinopathies and anemia
and less day-to-day perturbations during CATEGORIES OF INCREASED RISK
may be problematic. For patients with an FOR DIABETES (PREDIABETES)
stress and illness. However, these advan- abnormal hemoglobin but normal red blood
tages may be offset by the lower sensitiv- cell turnover, such as those with the sickle Recommendations
ity of A1C at the designated cut point, c Testing to assess risk for future di-
cell trait, an A1C assay without interference
greater cost, limited availability of A1C from abnormal hemoglobins should be abetes in asymptomatic people
testing in certain regions of the develop- used. An updated list of interferences is should be considered in adults of
ing world, and the imperfect correlation available at www.ngsp.org/interf.asp. any age who are overweight or
between A1C and average glucose in cer- obese (BMI $25 kg/m 2 or $23
Red Blood Cell Turnover kg/m 2 in Asian Americans) and
tain individuals. National Health and
Nutrition Examination Survey (NHANES) In conditions associated with increased who have one or more additional
data indicate that an A1C cut point of red blood cell turnover, such as pregnancy risk factors for diabetes. B
$6.5% (48 mmol/mol) identies one- (second and third trimesters), recent blood c For all patients, testing should begin
third fewer cases of undiagnosed diabe- loss or transfusion, erythropoietin therapy, at age 45 years. B
tes than a fasting glucose cut point of or hemolysis, only blood glucose criteria c If tests are normal, repeat testing
$126 mg/dL (7.0 mmol/L) (4). should be used to diagnose diabetes. carried out at a minimum of 3-year
It is important to take age, race/ intervals is reasonable. C
ethnicity, and anemia/hemoglobinop- Conrming the Diagnosis c To test for prediabetes, fasting
athies into consideration when using Unless there is a clear clinical diagnosis plasma glucose, 2-h plasma glucose
the A1C to diagnose diabetes. (e.g., patient in a hyperglycemic crisis or after 75-g oral glucose tolerance test,
Age
with classic symptoms of hyperglycemia and A1C are equally appropriate. B
and a random plasma glucose $200 c In patients with prediabetes, iden-
The epidemiological studies that formed
mg/dL [11.1 mmol/L]), a second test is re- tify and, if appropriate, treat other
the basis for recommending A1C to di-
agnose diabetes included only adult
quired for conrmation. It is recom- cardiovascular disease risk factors. B
mended that the same test be repeated c Testing to detect prediabetes should
populations. Therefore, it remains un-
without delay using a new blood sample be considered in children and ado-
clear if A1C and the same A1C cut point
for conrmation because there will be a lescents who are overweight or
should be used to diagnose diabetes in
greater likelihood of concurrence. For ex- obese and who have two or more
children and adolescents (4,5).
ample, if the A1C is 7.0% (53 mmol/mol) additional risk factors for diabetes. E
Race/Ethnicity and a repeat result is 6.8% (51 mmol/mol),
A1C levels may vary with patients race/ the diagnosis of diabetes is conrmed. If
ethnicity (6,7). For example, African Amer- two different tests (such as A1C and FPG) Description
icans may have higher A1C levels than are both above the diagnostic threshold, In 1997 and 2003, the Expert Committee
non-Hispanic whites despite similar fast- this also conrms the diagnosis. On the on the Diagnosis and Classication of Di-
ing and postglucose load glucose levels. other hand, if a patient has discordant abetes Mellitus (10,11) recognized a
African Americans also have higher levels results from two different tests, then group of individuals whose glucose
care.diabetesjournals.org
levels did not meet the criteria for di-
abetes but were too high to be consid-
ered normal. Prediabetes is the term
used for individuals with impaired fast-
ing glucose (IFG) and/or impaired glu-
cose tolerance (IGT) and indicates an
increased risk for the future develop-
ment of diabetes. IFG and IGT should
not be viewed as clinical entities in their
own right but rather risk factors for di-
abetes (Table 2.2) and cardiovascular
disease (CVD). IFG and IGT are associ-
ated with obesity (especially abdominal
or visceral obesity), dyslipidemia with
high triglycerides and/or low HDL cho-
lesterol, and hypertension.
Diagnosis
In 1997 and 2003, the Expert Committee
on the Diagnosis and Classication of Di-
abetes Mellitus (10,11) dened IFG as
FPG levels 100125 mg/dL (5.66.9
mmol/L) and IGT as 2-h PG after 75-g
OGTT levels 140199 mg/dL (7.811.0
mmol/L). It should be noted that the
World Health Organization (WHO) and
numerous diabetes organizations dene
the IFG cutoff at 110 mg/dL (6.1 mmol/L).
As with the glucose measures, several
prospective studies that used A1C to
predict the progression to diabetes
demonstrated a strong, continuous as-
sociation between A1C and subsequent
diabetes. In a systematic review of
44,203 individuals from 16 cohort stud-
ies with a follow-up interval averaging
5.6 years (range 2.812 years), those
with an A1C between 5.56.0% (3742
mmol/mol) had a substantially in-
creased risk of diabetes (5-year inci-
dence from 9% to 25%). An A1C range
of 6.06.5% (4248 mmol/mol) had a
5-year risk of developing diabetes be-
tween 25% and 50% and a relative
risk 20 times higher compared with an
A1C of 5.0% (31 mmol/mol) (12). In a
community-based study of African
American and non-Hispanic white adults
without diabetes, baseline A1C was a
stronger predictor of subsequent diabe-
tes and cardiovascular events than fast-
ing glucose (13). Other analyses suggest
that an A1C of 5.7% (39 mmol/mol) is
associated with a diabetes risk similar
to that of the high-risk participants in
the Diabetes Prevention Program (DPP)
(14), and A1C at baseline was a strong
predictor of the development of glucose-
dened diabetes during the DPP and its
follow-up (15).
Hence, it is reasonable to consider an
A1C range of 5.76.4% (3946 mmol/mol)
as identifying individuals with prediabe-
tes. As with those with IFG and/or IGT,
individuals with an A1C of 5.76.4%
(3946 mmol/mol) should be informed
of their increased risk for diabetes and
CVD and counseled about effective strate-
gies to lower their risks (see Section 4 Pre-
vention or Delay of Type 2 Diabetes).
Similar to glucose measurements, the con-
tinuum of risk is curvilinear, so as A1C rises,
the diabetes risk rises disproportionately
(12). Aggressive interventions and vigilant
follow-up should be pursued for those
considered at very high risk (e.g., those
with A1C .6.0% [42 mmol/mol]).
Table 2.3 summarizes the categories
of prediabetes and Table 2.2 the criteria
for prediabetes testing. For recommen-
dations regarding risk factors and
screening for prediabetes, see pp. S17
S18 (Testing for Type 2 Diabetes and Pre-
diabetes in Asymptomatic Adults and
Testing for Type 2 Diabetes and Pre-
diabetes in Children and Adolescents).
TYPE 1 DIABETES
Recommendations
c Blood glucose rather than A1C should
be used to diagnose acute onset of
type 1 diabetes in individuals with
symptoms of hyperglycemia. E
c Inform the relatives of patients with
type 1 diabetes of the opportunity
to be tested for type 1 diabetes risk,
but only in the setting of a clinical
research study. E
Diagnosis
In a patient with acute symptoms, mea-
surement of blood glucose is part of the
denition of diabetes (classic symptoms of
hyperglycemia or hyperglycemic crisis plus
a random plasma glucose $200 mg/dL
[11.1 mmol/L]). In these cases, knowing
the blood glucose level is critical because,
in addition to conrming that symptoms
are due to diabetes, this will inform man-
agement decisions. Some providers may
also want to know the A1C to determine
how long a patient has had hyperglycemia.
Immune-Mediated Diabetes
This form, previously called insulin-
dependent diabetes or juvenile-onset
diabetes, accounts for 510% of diabe-
tes and is due to cellular-mediated auto-
immune destruction of the pancreatic
b-cells. Autoimmune markers include
Classication and Diagnosis of Diabetes S15
islet cell autoantibodies and autoanti-
bodies to insulin, GAD (GAD65), the ty-
rosine phosphatases IA-2 and IA-2b, and
ZnT8. Type 1 diabetes is dened by one
or more of these autoimmune markers.
The disease has strong HLA associations,
with linkage to the DQA and DQB genes.
These HLA-DR/DQ alleles can be either
predisposing or protective.
The rate of b-cell destruction is quite
variable, being rapid in some individu-
als (mainly infants and children) and
slow in others (mainly adults). Children
and adolescents may present with ke-
toacidosis as the rst manifestation of
the disease. Others have modest fast-
ing hyperglycemia that can rapidly
change to severe hyperglycemia and/or
ketoacidosis with infection or other
stress. Adults may retain sufcient b-cell
function to prevent ketoacidosis for
many years; such individuals eventually
become dependent on insulin for survival
and are at risk for ketoacidosis. At this
latter stage of the disease, there is little
or no insulin secretion, as manifested by
low or undetectable levels of plasma C-
peptide. Immune-mediated diabetes
commonly occurs in childhood and ado-
lescence, but it can occur at any age, even
in the 8th and 9th decades of life.
Autoimmune destruction of b-cells
has multiple genetic predispositions
and is also related to environmental fac-
tors that are still poorly dened. Al-
though patients are not typically obese
when they present with type 1 diabetes,
obesity should not preclude the diagno-
sis. These patients are also prone to
other autoimmune disorders such as
Hashimoto thyroiditis, celiac disease,
Graves disease, Addison disease, viti-
ligo, autoimmune hepatitis, myasthenia
gravis, and pernicious anemia.
Idiopathic Type 1 Diabetes
Some forms of type 1 diabetes have no
known etiologies. These patients have
permanent insulinopenia and are prone
to ketoacidosis, but have no evidence of
b-cell autoimmunity. Although only a
minority of patients with type 1 diabetes
fall into this category, of those who do,
most are of African or Asian ancestry.
Individuals with this form of diabetes
suffer from episodic ketoacidosis and
exhibit varying degrees of insulin de-
ciency between episodes. This form of
diabetes is strongly inherited and is not
HLA associated. An absolute requirement
S16 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

Table 2.2Criteria for testing for diabetes or prediabetes in asymptomatic adults being conducted to test various meth-
1. Testing should be considered in all adults who are overweight (BMI $25 kg/m or $23 kg/m in
2 2 ods of preventing type 1 diabetes in
Asian Americans) and have additional risk factors: those with evidence of autoimmunity
c physical inactivity (www.clinicaltrials.gov).
c rst-degree relative with diabetes
c high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American,
TYPE 2 DIABETES
Pacic Islander)
c women who delivered a baby weighing .9 lb or were diagnosed with GDM Recommendations
c hypertension ($140/90 mmHg or on therapy for hypertension) c Testing to detect type 2 diabetes in
c HDL cholesterol level ,35 mg/dL (0.90 mmol/L) and/or a triglyceride level .250 mg/dL asymptomatic people should be con-
(2.82 mmol/L) sidered in adults of any age who are
c women with polycystic ovary syndrome
overweight or obese (BMI $25
c A1C $5.7% (39 mmol/mol), IGT, or IFG on previous testing
c other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis
kg/m2 or $23 kg/m2 in Asian Amer-
nigricans) icans) and who have one or more
c history of CVD additional risk factors for diabetes. B
2. For all patients, testing should begin at age 45 years. c For all patients, testing should be-
3. If results are normal, testing should be repeated at a minimum of 3-year intervals, with gin at age 45 years. B
consideration of more frequent testing depending on initial results (e.g., those with c If tests are normal, repeat testing
prediabetes should be tested yearly) and risk status. carried out at a minimum of 3-year
intervals is reasonable. C
c To test for type 2 diabetes, fasting
for insulin replacement therapy in af- type 1 diabetes within 10 years and 84% plasma glucose, 2-h plasma glucose
fected patients may be intermittent. within 15 years (19,20). These ndings are after 75-g oral glucose tolerance test,
highly signicant because, while the and A1C are equally appropriate. B
Testing for Type 1 Diabetes Risk German group was recruited from off- c In patients with diabetes, identify
The incidence and prevalence of type 1 spring of parents with type 1 diabetes, and, if appropriate, treat other car-
diabetes is increasing (16). Patients with the Finnish and American groups were diovascular disease risk factors. B
type 1 diabetes often present with acute recruited from the general population. c Testing to detect type 2 diabetes
symptoms of diabetes and markedly el- Remarkably, the ndings in all three should be considered in children
evated blood glucose levels, and ap- groups were the same, suggesting that and adolescents who are overweight
proximately one-third are diagnosed the same sequence of events led to clin- or obese and who have two or more
with life-threatening ketoacidosis (2). ical disease in both sporadic and famil- additional risk factors for diabetes. E
Several studies indicate that measuring ial cases of type 1 diabetes.
islet autoantibodies in relatives of those Although there is currently a lack of
Description
with type 1 diabetes may identify individ- accepted screening programs, one Type 2 diabetes, previously referred to
uals who are at risk for developing type 1 should consider referring relatives of as noninsulin-dependent diabetes or
diabetes (17). Such testing, coupled with those with type 1 diabetes for antibody adult-onset diabetes, accounts for
education about diabetes symptoms and testing for risk assessment in the setting 9095% of all diabetes. This form en-
close follow-up in an observational clini- of a clinical research study (http://www2 compasses individuals who have insulin
cal study, may enable earlier identica- .diabetestrialnet.org). Widespread clini- resistance and usually relative (rather
tion of type 1 diabetes onset (18). There cal testing of asymptomatic low-risk in- than absolute) insulin deciency. At
is evidence to suggest that early diagnosis dividuals is not currently recommended least initially, and often throughout
may limit acute complications (19). due to lack of approved therapeutic in- their lifetime, these individuals may
A recent study reported the risk of pro- terventions. Higher-risk individuals may not need insulin treatment to survive.
gression to type 1 diabetes from the be tested, but only in the context of a There are various causes of type 2 di-
time of seroconversion to autoantibody clinical research setting. Individuals abetes. Although the specic etiologies
positivity in three pediatric cohorts from who test positive will be counseled are not known, autoimmune destruction
Finland, Germany, and the U.S. Of the 585 about the risk of developing diabetes, of b-cells does not occur, and patients do
children who developed more than two diabetes symptoms, and DKA preven- not have any of the other known causes
autoantibodies, nearly 70% developed tion. Numerous clinical studies are of diabetes. Most, but not all, patients
with type 2 diabetes are overweight or
Table 2.3Categories of increased risk for diabetes (prediabetes)* obese. Excess weight itself causes some
FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG) degree of insulin resistance. Patients who
OR are not obese or overweight by traditional
2-h PG in the 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT) weight criteria may have an increased
OR
percentage of body fat distributed pre-
dominantly in the abdominal region.
A1C 5.76.4% (3946 mmol/mol)
Ketoacidosis seldom occurs sponta-
*For all three tests, risk is continuous, extending below the lower limit of the range and neously in type 2 diabetes; when seen,
becoming disproportionately greater at the higher end of the range.
it usually arises in association with the
care.diabetesjournals.org
stress of another illness such as infec-
tion. Type 2 diabetes frequently goes
undiagnosed for many years because hy-
perglycemia develops gradually and, at
earlier stages, is often not severe enough
for the patient to notice the classic diabe-
tes symptoms. Nevertheless, even undi-
agnosed patients are at increased risk of
developing macrovascular and microvas-
cular complications.
Whereas patients with type 2 diabetes
may have insulin levels that appear nor-
mal or elevated, the higher blood glucose
levels in these patients would be expected
to result in even higher insulin values had
their b-cell function been normal. Thus,
insulin secretion is defective in these pa-
tients and insufcient to compensate for
insulin resistance. Insulin resistance may
improve with weight reduction and/or
pharmacological treatment of hypergly-
cemia but is seldom restored to normal.
The risk of developing type 2 diabetes
increases with age, obesity, and lack of
physical activity. It occurs more fre-
quently in women with prior GDM, in
those with hypertension or dyslipidemia,
and in certain racial/ethnic subgroups
(African American, American Indian,
Hispanic/Latino, and Asian American). It
is often associated with a strong genetic
predisposition, more so than type 1 dia-
betes. However, the genetics of type 2
diabetes is poorly understood.
Testing for Type 2 Diabetes and
Prediabetes in Asymptomatic Adults
Prediabetes and type 2 diabetes meet cri-
teria for conditions in which early detec-
tion is appropriate. Both conditions are
common and impose signicant clinical
and public health burdens. There is often
a long presymptomatic phase before the
diagnosis of type 2 diabetes. Simple tests
to detect preclinical disease are readily
available. The duration of glycemic burden
is a strong predictor of adverse outcomes.
There are effective interventions that pre-
vent progression from prediabetes to dia-
betes (see Section 4 Prevention or Delay
of Type 2 Diabetes) and reduce the risk of
diabetes complications (see Section 8
Cardiovascular Disease and Risk Man-
agement and Section 9 Microvascular
Complications and Foot Care).
Approximately one-quarter of people
with diabetes in the U.S. and nearly half
of Asian and Hispanic Americans with
diabetes are undiagnosed (21). Al-
though screening of asymptomatic
individuals to identify those with predi-
abetes or diabetes might seem reason-
able, rigorous clinical trials to prove the
effectiveness of such screening have not
been conducted and are unlikely to occur.
A large European randomized con-
trolled trial compared the impact of
screening for diabetes and intensive
multifactorial intervention with that of
screening and routine care (22). General
practice patients between the ages of
4069 years were screened for diabetes
and randomly assigned by practice to
intensive treatment of multiple risk fac-
tors or routine diabetes care. After 5.3
years of follow-up, CVD risk factors were
modestly but signicantly improved
with intensive treatment compared
with routine care, but the incidence of
rst CVD events or mortality was not
signicantly different between the
groups (22). The excellent care provided
to patients in the routine care group and
the lack of an unscreened control arm
limited the authors ability to prove that
screening and early intensive treatment
impact outcomes. Mathematical model-
ing studies suggest that major benets
are likely to accrue from the early diag-
nosis and treatment of glycemia and car-
diovascular risk factors in type 2 diabetes
(23); moreover, screening, beginning at
age 30 or 45 years and independent
of risk factors, may be cost-effective
(,$11,000 per quality-adjusted life-
year gained) (24).
Additional considerations regarding
testing for type 2 diabetes and predia-
betes in asymptomatic patients include
the following:
Age
Testing recommendations for diabetes
in asymptomatic adults are listed in
Table 2.2. Age is a major risk factor for
diabetes. Testing should begin at age 45
years for all patients.
BMI and Ethnicity
Testing should be considered in adults
of any age with BMI $25 kg/m2 and one
or more additional risk factors for dia-
betes. However, recent data (25) and
evidence from the ADA position state-
ment BMI Cut Points to Identify At-Risk
Asian Americans for Type 2 Diabetes
Screening (26) suggest that the BMI
cut point should be lower for the Asian
American population. For diabetes
screening purposes, the BMI cut points
fall consistently between 23 and 24 kg/m2
Classication and Diagnosis of Diabetes S17
(sensitivity of 80%) for nearly all Asian
American subgroups (with levels slightly
lower for Japanese Americans). This
makes a rounded cut point of 23 kg/m2
practical. In determining a single BMI cut
point, it is important to balance sensitivity
and specicity so as to provide a valuable
screening tool without numerous false
positives. An argument can be made to
push the BMI cut point to lower than
23 kg/m2 in favor of increased sensitivity;
however, this would lead to an unaccept-
ably low specicity (13.1%). Data from the
WHO also suggest that a BMI $23 kg/m2
should be used to dene increased risk
in Asian Americans (27). The nding
that half of diabetes in Asian Americans
is undiagnosed suggests that testing is not
occurring at lower BMI thresholds (21).
Evidence also suggests that other
populations may benet from lower
BMI cut points. For example, in a large
multiethnic cohort study, for an equiva-
lent incidence rate of diabetes, a BMI of
30 kg/m2 in non-Hispanic whites was
equivalent to a BMI of 26 kg/m2 in Afri-
can Americans (28).
Medications
Certain medications, such as glucocorti-
coids, thiazide diuretics, and atypical an-
tipsychotics (29), are known to increase
the risk of diabetes and should be con-
sidered when ascertaining a diagnosis.
Diagnostic Tests
FPG, 2-h PG after 75-g OGTT, and A1C
are equally appropriate for testing. It
should be noted that the tests do not
necessarily detect diabetes in the same
individuals. The efcacy of interventions
for primary prevention of type 2 diabe-
tes (30,31) has primarily been demon-
strated among individuals with IGT, not
for individuals with isolated IFG or for
those with prediabetes dened by A1C
criteria.
Testing Interval
The appropriate interval between tests is
not known (32). The rationale for the
3-year interval is that with this interval,
the number of false-positive tests that re-
quire conrmatory testing will be reduced
and individuals with false-negative tests
will be retested before substantial time
elapses and complications develop (32).
Community Screening
Ideally, testing should be carried out
within a health care setting because of
the need for follow-up and treatment.
S18 Classication and Diagnosis of Diabetes
Community testing outside a health care
setting is not recommended because
people with positive tests may not
seek, or have access to, appropriate
follow-up testing and care. Community
testing may also be poorly targeted; i.e.,
it may fail to reach the groups most at
risk and inappropriately test those at
very low risk or even those who have
already been diagnosed.
Testing for Type 2 Diabetes and
Prediabetes in Children and
Adolescents
In the last decade, the incidence and
prevalence of type 2 diabetes in ado-
lescents has increased dramatically, es-
pecially in ethnic populations (16).
Recent studies question the validity of
A1C in the pediatric population, espe-
cially among certain ethnicities, and
suggest OGTT or FPG as more suitable
diagnostic tests (33). However, many of
these studies do not recognize that di-
abetes diagnostic criteria are based on
long-term health outcomes, and valida-
tions are not currently available in the
pediatric population (34). The ADA ac-
knowledges the limited data support-
ing A1C for diagnosing type 2 diabetes
in children and adolescents. Although
A1C is not recommended for diagnosis
of diabetes in children with cystic bro-
sis or symptoms suggestive of acute on-
set of type 1 diabetes and only A1C
assays without interference are appro-
priate for children with hemoglobinopa-
thies, the ADA continues to recommend
A1C for diagnosis of type 2 diabetes in
this cohort (35,36). The modied recom-
mendations of the ADA consensus
report Type 2 Diabetes in Children
and Adolescents are summarized in
Table 2.4.
GESTATIONAL DIABETES
MELLITUS
Recommendations
c Test for undiagnosed type 2 diabe-
tes at the rst prenatal visit in
those with risk factors, using stan-
dard diagnostic criteria. B
c Test for gestational diabetes mel-
litus at 2428 weeks of gestation
in pregnant women not previously
known to have diabetes. A
c Screen women with gestational di-
abetes mellitus for persistent diabe-
tes at 612 weeks postpartum,
Diabetes Care Volume 39, Supplement 1, January 2016
using the oral glucose tolerance
test and clinically appropriate non-
pregnancy diagnostic criteria. E
c Women with a history of gesta-
tional diabetes mellitus should
have lifelong screening for the de-
velopment of diabetes or predia-
betes at least every 3 years. B
c Women with a history of gesta-
tional diabetes mellitus found to
have prediabetes should receive
lifestyle interventions or metfor-
min to prevent diabetes. A
Denition
For many years, GDM was dened as any
degree of glucose intolerance that was rst
recognized during pregnancy (10), regard-
less of whether the condition may have pre-
dated the pregnancy or persisted after the
pregnancy. This denition facilitated a uni-
form strategy for detection and classication
of GDM, but it was limited by imprecision.
The ongoing epidemic of obesity and
diabetes has led to more type 2 diabetes
in women of childbearing age, with an in-
crease in the number of pregnant women
with undiagnosed type 2 diabetes (37). Be-
cause of the number of pregnant women
with undiagnosed type 2 diabetes, it is rea-
sonable to test women with risk factors for
type 2 diabetes (Table 2.2) at their initial
prenatal visit, using standard diagnostic
criteria (Table 2.1). Women with diabetes
in the rst trimester would be classied as
having type 2 diabetes. GDM is diabetes
diagnosed in the second or third trimester
of pregnancy that is not clearly either
type 1 or type 2 diabetes (see Section 12
Management of Diabetes in Pregnancy).
Diagnosis
GDM carries risks for the mother and ne-
onate. Not all adverse outcomes are of
equal clinical importance. The Hypergly-
cemia and Adverse Pregnancy Outcome
(HAPO) study (38), a large-scale (25,000
pregnant women) multinational cohort
study, demonstrated that risk of adverse
maternal, fetal, and neonatal outcomes
continuously increased as a function of
maternal glycemia at 2428 weeks, even
within ranges previously considered nor-
mal for pregnancy. For most complica-
tions, there was no threshold for risk.
These results have led to careful reconsid-
eration of the diagnostic criteria for GDM.
GDM diagnosis (Table 2.5) can be accom-
plished with either of two strategies:
1. One-step 75-g OGTT or
2. Two-step approach with a 50-g (non-
fasting) screen followed by a 100-g
OGTT for those who screen positive
Different diagnostic criteria will identify
different degrees of maternal hyperglyce-
mia and maternal/fetal risk, leading some
experts to debate, and disagree on, opti-
mal strategies for the diagnosis of GDM.
One-Step Strategy
In the 2011 Standards of Care (39), the
ADA for the rst time recommended
that all pregnant women not known to
have prior diabetes undergo a 75-g
OGTT at 2428 weeks of gestation, based
on a recommendation of the Interna-
tional Association of the Diabetes and
Pregnancy Study Groups (IADPSG) (40).
The IADPSG dened diagnostic cut points
for GDM as the average glucose values
(fasting, 1-h, and 2-h PG) in the HAPO
study at which odds for adverse out-
comes reached 1.75 times the estimated
odds of these outcomes at the mean glu-
cose levels of the study population. This
one-step strategy was anticipated to sig-
nicantly increase the incidence of GDM
(from 56% to 1520%), primarily be-
cause only one abnormal value, not two,
became sufcient to make the diagnosis.
The ADA recognized that the anticipated
increase in the incidence of GDM would
have signicant impact on the costs, med-
ical infrastructure capacity, and potential
for increased medicalization of preg-
nancies previously categorized as normal,
but recommended these diagnostic crite-
ria changes in the context of worrisome
worldwide increases in obesity and diabe-
tes rates with the intent of optimizing
gestational outcomes for women and
their offspring.
The expected benets to these preg-
nancies and offspring are inferred from
intervention trials that focused on
women with lower levels of hyperglyce-
mia than identied using older GDM di-
agnostic criteria and that found modest
benets including reduced rates of
large-for-gestational-age births and pre-
eclampsia (41,42). It is important to
note that 8090% of women being
treated for mild GDM in two random-
ized controlled trials (whose glucose val-
ues overlapped with the thresholds
recommended by the IADPSG) could
be managed with lifestyle therapy
alone. Data are lacking on how the
care.diabetesjournals.org
Table 2.4Testing for type 2 diabetes or prediabetes in asymptomatic children*
Criteria
c Overweight (BMI .85th percentile for age and sex, weight for height .85th percentile, or
weight .120% of ideal for height)
Plus any two of the following risk factors:
c Family history of type 2 diabetes in rst- or second-degree relative
c Race/ethnicity (Native American, African American, Latino, Asian American, Pacic Islander)
c Signs of insulin resistance or conditions associated with insulin resistance (acanthosis
nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small-for-gestational-
age birth weight)
c Maternal history of diabetes or GDM during the childs gestation
Age of initiation: age 10 years or at onset of puberty, if puberty occurs at a younger age
Frequency: every 3 years
*Persons aged #18 years.
treatment of lower levels of hyperglyce-
mia affects a mothers risk for the devel-
opment of type 2 diabetes in the future
and her offsprings risk for obesity, di-
abetes, and other metabolic dysfunc-
tion. Additional well-designed clinical
studies are needed to determine the op-
timal intensity of monitoring and treat-
ment of women with GDM diagnosed by
the one-step strategy.
Two-Step Strategy
In 2013, the National Institutes of Health
(NIH) convened a consensus develop-
ment conference on diagnosing GDM.
The 15-member panel had representatives
from obstetrics/gynecology, maternal-
fetal medicine, pediatrics, diabetes re-
search, biostatistics, and other related
elds to consider diagnostic criteria (43).
The panel recommended the two-step
approach of screening with a 1-h 50-g
glucose load test (GLT) followed by a 3-h
100-g OGTT for those who screen posi-
tive, a strategy commonly used in the U.S.
Key factors reported in the NIH pan-
els decision-making process were the
lack of clinical trial interventions dem-
onstrating the benets of the one-step
strategy and the potential negative con-
sequences of identifying a large new
group of women with GDM, including
medicalization of pregnancy with in-
creased interventions and costs. More-
over, screening with a 50-g GLT does not
require fasting and is therefore easier to
accomplish for many women. Treat-
ment of higher threshold maternal
hyperglycemia, as identied by the two-
step approach, reduces rates of neonatal
macrosomia, large-for-gestational-age
births (44), and shoulder dystocia, with-
out increasing small-for-gestational-age
births. The American College of Obstetri-
cians and Gynecologists (ACOG) updated
its guidelines in 2013 and supported the
two-step approach (45).
Future Considerations
The conicting recommendations from
expert groups underscore the fact that
there are data to support each strategy.
The decision of which strategy to imple-
ment must therefore be made based on
the relative values placed on factors that
have yet to be measured (e.g., costbenet
estimation, willingness to change prac-
tice based on correlation studies rather
than clinical intervention trial results, rel-
ative role of cost considerations, and avail-
able infrastructure locally, nationally, and
internationally).
As the IADPSG criteria have been adop-
ted internationally, further evidence has
emerged to support improved pregnancy
outcomes with cost savings (46) and may
be the preferred approach. In addition,
pregnancies complicated by GDM per
IADPSG criteria, but not recognized as
such, have comparable outcomes to preg-
nancies diagnosed as GDM by the more
stringent two-step criteria (47). There
remains strong consensus that estab-
lishing a uniform approach to diagnosing
GDM will benet patients, caregivers,
and policymakers. Longer-term outcome
studies are currently under way.
MONOGENIC DIABETES
SYNDROMES
Recommendations
c All children diagnosed with diabe-
tes in the rst 6 months of life
should have genetic testing. B
c Maturity-onset diabetes of the
young should be considered in indi-
viduals who have mild stable fasting
hyperglycemia and multiple family
members with diabetes not charac-
teristic of type 1 or type 2 diabetes. E
Classication and Diagnosis of Diabetes S19
c Because a diagnosis of maturity-
onset diabetes of the young may
impact therapy and lead to identi-
cation of other affected family
members, consider referring indi-
viduals with diabetes not typical of
type 1 or type 2 diabetes and oc-
curing in successive generations
(suggestive of an autosomal dom-
inant pattern of inheritance) to a
specialist for further evaluation. E
Monogenic defects that cause b-cell
dysfunction, such as neonatal diabetes
and MODY, represent a small fraction of
patients with diabetes (,5%). These
forms of diabetes are frequently charac-
terized by onset of hyperglycemia at an
early age (generally before age 25 years).
Neonatal Diabetes
Neonatal diabetes is a monogenic form of
diabetes with onset in the rst 6 months of
life. It can be mistaken for the more com-
mon type 1 diabetes, but type 1 diabetes
rarely occurs before 6 months of age. Neo-
natal diabetes can either be transient or
permanent. The most common genetic
defect causing transient disease is a defect
on ZAC/HYAMI imprinting, whereas per-
manent neonatal diabetes is most com-
monly an autosomal dominant defect in
the gene encoding the Kir6.2 subunit of
the b-cell KATP channel. Correct diagnosis
has important implications, because chil-
dren with neonatal diabetes due to muta-
tions affecting Kir6.2 should be treated
with sulfonylureas rather than insulin.
Maturity-Onset Diabetes of the Young
MODY is characterized by impaired insulin
secretion with minimal or no defects in
insulin action. It is inherited in an autoso-
mal dominant pattern. Abnormalities at
six genetic loci on different chromosomes
have been identied to date. The most
common form (MODY 3) is associated
with mutations on chromosome 12 in a
hepatic transcription factor referred to as
hepatocyte nuclear factor (HNF)-1a and
also referred to as transcription factor-1
(TCF-1). The second most common form
(MODY 2) is associated with mutations in
the glucokinase gene on chromosome 7p
and results in a defective glucokinase mol-
ecule. Glucokinase converts glucose to
glucose-6-phosphate, the metabolism of
which, in turn, stimulates insulin secretion
by the b-cell. The less common forms of
MODY result from mutations in other
S20 Classication and Diagnosis of Diabetes Diabetes Care Volume 39, Supplement 1, January 2016

Table 2.5Screening for and diagnosis of GDM occurring in about 20% of adolescents
One-step strategy
and 4050% of adults. Diabetes in this
Perform a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and
population, compared with individuals
2 h, at 2428 weeks of gestation in women not previously diagnosed with overt diabetes. with type 1 or type 2 diabetes, is asso-
The OGTT should be performed in the morning after an overnight fast of at least 8 h. ciated with worse nutritional status,
The diagnosis of GDM is made when any of the following plasma glucose values are met or more severe inammatory lung dis-
exceeded: ease, and greater mortality. Insulin in-
c Fasting: 92 mg/dL (5.1 mmol/L) sufciency is the primary defect in
c 1 h: 180 mg/dL (10.0 mmol/L) CFRD. Genetically determined b-cell
c 2 h: 153 mg/dL (8.5 mmol/L) function and insulin resistance associ-
Two-step strategy ated with infection and inammation
Step 1: Perform a 50-g GLT (nonfasting), with plasma glucose measurement at 1 h, at 2428 may also contribute to the develop-
weeks of gestation in women not previously diagnosed with overt diabetes. ment of CFRD. Milder abnormalities
If the plasma glucose level measured 1 h after the load is $140 mg/dL* (7.8 mmol/L), proceed of glucose tolerance are even more
to a 100-g OGTT.
common and occur at earlier ages
Step 2: The 100-g OGTT should be performed when the patient is fasting. than CFRD. Although screening for di-
The diagnosis of GDM is made if at least two of the following four plasma glucose levels abetes before the age of 10 years can
(measured fasting and 1 h, 2 h, 3 h after the OGTT) are met or exceeded:
identify risk for progression to CFRD
Carpenter/Coustan (55) or NDDG (56) in those with abnormal glucose toler-
cFasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L) ance, no benet has been established
c1h 180 mg/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L) with respect to weight, height, BMI,
c2h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L) or lung function. Continuous glucose
c3h 140 mg/dL (7.8 mmol/L) 145 mg/dL (8.0 mmol/L) monitoring may be more sensitive
NDDG, National Diabetes Data Group. *The ACOG recommends a lower threshold of 135 mg/dL than OGTT to detect risk for progres-
(7.5 mmol/L) in high-risk ethnic populations with higher prevalence of GDM; some experts also sion to CFRD, but evidence linking
recommend 130 mg/dL (7.2 mmol/L). continuous glucose monitoring results
to long-term outcomes is lacking
transcription factors, including HNF-4a, without typical clinical features of and its use is not recommended for
HNF-1b, insulin promoter factor-1 (IPF-1), type 2 diabetes screening (50).
and NeuroD1. CRFD mortality has signicantly de-
Diagnosis CYSTIC FIBROSISRELATED creased over time, and the gap in mor-
A diagnosis of MODY should be consid- DIABETES tality between cystic brosis patients
ered in individuals who have atypical di- Recommendations with and without diabetes has consider-
abetes and multiple family members c Annual screening for cystic brosis ably narrowed (51). There are limited
with diabetes not characteristic of related diabetes with oral glucose clinical trial data on therapy for CFRD.
type 1 or type 2 diabetes. These individ- tolerance test should begin by age The largest study compared three regi-
uals should be referred to a specialist for 10 years in all patients with cystic mens: premeal insulin aspart, repagli-
further evaluation. Readily available brosis who do not have cystic nide, or oral placebo in cystic brosis
commercial genetic testing now enables brosisrelated diabetes. B patients with diabetes or abnormal
a genetic diagnosis. It is important to cor- c A1C as a screening test for cystic glucose tolerance. Participants all had
rectly diagnose one of the monogenic brosisrelated diabetes is not weight loss in the year preceding treat-
forms of diabetes because these patients recommended. B ment; however, in the insulin-treated
may be incorrectly diagnosed with type 1 c Patients with cystic brosisrelated group, this pattern was reversed, and
or type 2 diabetes, leading to suboptimal diabetes should be treated with patients gained 0.39 (6 0.21) BMI units
treatment regimens and delays in diag- insulin to attain individualized gly- (P 5 0.02). The repaglinide-treated
nosing other family members (48,49). cemic goals. A group had initial weight gain, but this
The diagnosis of monogenic diabetes c In patients with cystic brosis and was not sustained by 6 months. The pla-
should be considered in children with impaired glucose tolerance with- cebo group continued to lose weight
the following ndings: out conrmed diabetes, prandial (52). Insulin remains the most widely
insulin therapy should be consid- used therapy for CFRD (53).
Diabetes diagnosed within the rst ered to maintain weight. B Recommendations for the clinical
6 months of life c Beginning 5 years after the diagnosis management of CFRD can be found in
Strong family history of diabetes but with- of cystic brosisrelated diabetes, the ADA position statement Clinical
out typical features of type 2 diabetes annual monitoring for complications Care Guidelines for Cystic Fibrosis
(nonobese, low-risk ethnic group) of diabetes is recommended. E Related Diabetes: A Position Statement
Mild fasting hyperglycemia (100150 of the American Diabetes Association
mg/dL [5.58.5 mmol/L]), especially if and a Clinical Practice Guideline of
young and nonobese Cystic brosisrelated diabetes the Cystic Fibrosis Foundation, En-
Diabetes with negative diabetes- (CFRD) is the most common comor- dorsed by the Pediatric Endocrine
associated autoantibodies and bidity in people with cystic brosis, Society (54).
care.diabetesjournals.org
References
1. American Diabetes Association. Diagnosis
and classication of diabetes mellitus. Diabetes
Care 2014;37(Suppl. 1):S81S90
2. Dabelea D, Rewers A, Stafford JM, et al.;
SEARCH for Diabetes in Youth Study Group.
Trends in the prevalence of ketoacidosis at di-
abetes diagnosis: the SEARCH for Diabetes in
Youth study. Pediatrics 2014;133:e938-e945
3. International Expert Committee. Interna-
tional Expert Committee report on the role of
the A1C assay in the diagnosis of diabetes. Di-
abetes Care 2009;32:13271334
4. Cowie CC, Rust KF, Byrd-Holt DD, et al. Prev-
alence of diabetes and high risk for diabetes
using A1C criteria in the U.S. population in
1988-2006. Diabetes Care 2010;33:562568
5. Nowicka P, Santoro N, Liu H, et al. Utility of
hemoglobin A1c for diagnosing prediabetes and
diabetes in obese children and adolescents. Di-
abetes Care 2011;34:13061311
6. Ziemer DC, Kolm P, Weintraub WS, et al.
Glucose-independent, black-white differences in
hemoglobin A1c levels: a cross-sectional analysis
of 2 studies. Ann Intern Med 2010;152:770777
7. Kumar PR, Bhansali A, Ravikiran M, et al. Util-
ity of glycated hemoglobin in diagnosing type
2 diabetes mellitus: a community-based study.
J Clin Endocrinol Metab 2010;95:28322835
8. Selvin E, Steffes MW, Ballantyne CM,
Hoogeveen RC, Coresh J, Brancati FL. Racial dif-
ferences in glycemic markers: a cross-sectional
analysis of community-based data. Ann Intern
Med 2011;154:303309
9. Selvin E, Rawlings AM, Bergenstal RM,
Coresh J, Brancati FL. No racial differences in
the association of glycated hemoglobin with
kidney disease and cardiovascular outcomes.
Diabetes Care 2013;36:29953001
10. Expert Committee on the Diagnosis and
Classication of Diabetes Mellitus. Report of
the Expert Committee on the Diagnosis and
Classication of Diabetes Mellitus. Diabetes
Care 1997;20:11831197
11. Genuth S, Alberti KG, Bennett P, et al.; Expert
Committee on the Diagnosis and Classication of
Diabetes Mellitus. Follow-up report on the diag-
nosis of diabetes mellitus. Diabetes Care 2003;26:
31603167
12. Zhang X, Gregg EW, Williamson DF, et al.
A1C level and future risk of diabetes: a system-
atic review. Diabetes Care 2010;33:16651673
13. Selvin E, Steffes MW, Zhu H, et al. Glycated
hemoglobin, diabetes, and cardiovascular risk
in nondiabetic adults. N Engl J Med 2010;362:
800811
14. Ackermann RT, Cheng YJ, Williamson DF,
Gregg EW. Identifying adults at high risk for di-
abetes and cardiovascular disease using hemo-
globin A1c National Health and Nutrition
Examination Survey 2005-2006. Am J Prev
Med 2011;40:1117
15. Diabetes Prevention Program Research
Group. HbA1c as a predictor of diabetes and
as an outcome in the Diabetes Prevention Pro-
gram: a randomized clinical trial. Diabetes Care
2015;38:5158
16. Dabelea D, Mayer-Davis EJ, Saydah S, et al.;
SEARCH for Diabetes in Youth Study. Prevalence
of type 1 and type 2 diabetes among children
and adolescents from 2001 to 2009. JAMA 2014;
311:17781786
17. Insel RA, Dunne JL, Atkinson MA, et al. Stag-
ing presymptomatic type 1 diabetes: a scientic
statement of JDRF, the Endocrine Society, and
the American Diabetes Association. Diabetes
Care 2015;38:19641974
18. Sosenko JM, Skyler JS, DiMeglio LA, et al.;
Type 1 Diabetes TrialNet Study Group; Diabetes
Prevention Trial-Type 1 Study Group. A new ap-
proach for diagnosing type 1 diabetes in auto-
antibody-positive individuals based on prediction
and natural history. Diabetes Care 2015;38:
271276
19. Ziegler AG, Rewers M, Simell O, et al. Sero-
conversion to multiple islet autoantibodies and
risk of progression to diabetes in children. JAMA
2013;309:24732479
20. Sosenko JM, Skyler JS, Palmer JP, et al.;
Type 1 Diabetes TrialNet Study Group; Diabetes
Prevention Trial-Type 1 Study Group. The pre-
diction of type 1 diabetes by multiple autoanti-
body levels and their incorporation into an
autoantibody risk score in relatives of type 1
diabetic patients. Diabetes Care 2013;36:
26152620
21. Menke A, Casagrande S, Geiss L, Cowie CC.
Prevalence of and trends in diabetes among
adults in the United States, 1988-2012. JAMA
2015;314:10211029
22. Grifn SJ, Borch-Johnsen K, Davies MJ, et al.
Effect of early intensive multifactorial therapy
on 5-year cardiovascular outcomes in individu-
als with type 2 diabetes detected by screening
(ADDITION-Europe): a cluster-randomised trial.
Lancet 2011;378:156167
23. Herman WH, Ye W, Grifn SJ, et al. Early
detection and treatment of type 2 diabetes re-
duce cardiovascular morbidity and mortality: a
simulation of the results of the Anglo-Danish-
Dutch Study of Intensive Treatment in People
With Screen-Detected Diabetes in Primary Care
(ADDITION-Europe). Diabetes Care 2015;38:
14491455
24. Kahn R, Alperin P, Eddy D, et al. Age at ini-
tiation and frequency of screening to detect
type 2 diabetes: a cost-effectiveness analysis.
Lancet 2010;375:13651374
25. Araneta MR, Kanaya AM, Hsu WC, et al. Opti-
mum BMI cut points to screen Asian Americans for
type 2 diabetes. Diabetes Care 2015;38:814820
26. Hsu WC, Araneta MR, Kanaya AM, Chiang
JL, Fujimoto W. BMI cut points to identify at-risk
Asian Americans for type 2 diabetes screening.
Diabetes Care 2015;38:150158
27. WHO Expert Consultation. Appropriate
body-mass index for Asian populations and its
implications for policy and intervention strate-
gies. Lancet 2004;363:157163
28. Chiu M, Austin PC, Manuel DG, Shah BR, Tu
JV. Deriving ethnic-specic BMI cutoff points for
assessing diabetes risk. Diabetes Care 2011;34:
17411748
29. Erickson SC, Le L, Zakharyan A, et al. New-
onset treatment-dependent diabetes mellitus
and hyperlipidemia associated with atypical an-
tipsychotic use in older adults without schizo-
phrenia or bipolar disorder. J Am Geriatr Soc
2012;60:474479
30. Knowler WC, Barrett-Connor E, Fowler SE,
et al.; Diabetes Prevention Program Research
Group. Reduction in the incidence of type 2 di-
abetes with lifestyle intervention or metformin.
N Engl J Med 2002;346:393403
Classication and Diagnosis of Diabetes S21
31. Tuomilehto J, Lindstr o m J, Eriksson JG,
et al.; Finnish Diabetes Prevention Study Group.
Prevention of type 2 diabetes mellitus by
changes in lifestyle among subjects with im-
paired glucose tolerance. N Engl J Med 2001;
344:13431350
32. Johnson SL, Tabaei BP, Herman WH. The
efcacy and cost of alternative strategies for
systematic screening for type 2 diabetes in the
U.S. population 45-74 years of age. Diabetes
Care 2005;28:307311
33. Buse JB, Kaufman FR, Linder B, Hirst K, El
Ghormli L, Willi S; HEALTHY Study Group. Diabetes
screening with hemoglobin A1c versus fasting
plasma glucose in a multiethnic middle-school co-
hort. Diabetes Care 2013;36:429435
34. Kapadia C, Zeitler P; Drugs and Therapeutics
Committee of the Pediatric Endocrine Society.
Hemoglobin A1c measurement for the diagnosis
of type 2 diabetes in children. Int J Pediatr En-
docrinol 2012;2012:31
35. Kester LM, Hey H, Hannon TS. Using hemo-
globin A1c for prediabetes and diabetes diagno-
sis in adolescents: can adult recommendations
be upheld for pediatric use? J Adolesc Health
2012;50:321323
36. Wu E-L, Kazzi NG, Lee JM. Cost-effectiveness
of screening strategies for identifying pediatric di-
abetes mellitus and dysglycemia. JAMA Pediatr
2013;167:3239
37. Lawrence JM, Contreras R, Chen W, Sacks
DA. Trends in the prevalence of preexisting di-
abetes and gestational diabetes mellitus
among a racially/ethnically diverse population
of pregnant women, 1999-2005. Diabetes Care
2008;31:899904
38. Metzger BE, Lowe LP, Dyer AR, et al.; HAPO
Study Cooperative Research Group. Hyperglyce-
mia and adverse pregnancy outcomes. N Engl J
Med 2008;358:19912002
39. American Diabetes Association. Standards
of medical care in diabetesd2011. Diabetes
Care 2011;34(Suppl. 1):S11S61
40. Metzger BE, Gabbe SG, Persson B, et al.;
International Association of Diabetes and
Pregnancy Study Groups Consensus Panel.
International Association of Diabetes and
Pregnancy Study Groups recommendations
on the diagnosis and classication of hyper-
glycemia in pregnancy. Diabetes Care 2010;
33:676682
41. Landon MB, Spong CY, Thom E, et al.; Eunice
Kennedy Shriver National Institute of Child
Health and Human Development Maternal-Fetal
Medicine Units Network. A multicenter, ran-
domized trial of treatment for mild gestational
diabetes. N Engl J Med 2009;361:13391348
42. Crowther CA, Hiller JE, Moss JR, McPhee AJ,
Jeffries WS, Robinson JS; Australian Carbohy-
drate Intolerance Study in Pregnant Women
(ACHOIS) Trial Group. Effect of treatment of
gestational diabetes mellitus on pregnancy out-
comes. N Engl J Med 2005;352:24772486
43. Vandorsten JP, Dodson WC, Espeland MA,
et al. NIH consensus development confer-
ence: diagnosing gestational diabetes melli-
tus. NIH Consens State Sci Statements 2013;
29:131
44. Horvath K, Koch K, Jeitler K, et al. Effects of
treatment in women with gestational diabetes
mellitus: systematic review and meta-analysis.
BMJ 2010;340:c1395
S22 Classication and Diagnosis of Diabetes
45. Committee on Practice BulletinsObstetrics.
Practice Bulletin No. 137: gestational diabetes
mellitus. Obstet Gynecol 2013;122:406416
46. Duran A, Saenz S, Torrejon MJ, et al. Intro-
duction of IADPSG criteria for the screening and
diagnosis of gestational diabetes mellitus re-
sults in improved pregnancy outcomes at a
lower cost in a large cohort of pregnant women:
the St. Carlos Gestational Diabetes Study.
Diabetes Care 2014;37:24422450
47. Ethridge JK Jr, Catalano PM, Waters TP. Peri-
natal outcomes associated with the diagnosis of
gestational diabetes made by the International
Association of the Diabetes and Pregnancy Study
Groups criteria. Obstet Gynecol 2014;124:571
578
48. Hattersley A, Bruining J, Shield J, Njolstad P,
Donaghue KC. The diagnosis and management of
monogenic diabetes in children and adolescents.
Pediatr Diabetes 2009;10(Suppl. 12):3342
Diabetes Care Volume 39, Supplement 1, January 2016
49. Rubio-Cabezas O, Hattersley AT, Njlstad
PR, et al.; International Society for Pediatric
and Adolescent Diabetes. ISPAD Clinical Practice
Consensus Guidelines 2014. The diagnosis and
management of monogenic diabetes in children
and adolescents. Pediatr Diabetes 2014;15
(Suppl. 20):4764
50. Ode KL, Moran A. New insights into cystic
brosis-related diabetes in children. Lancet Di-
abetes Endocrinol 2013;1:5258
51. Moran A, Dunitz J, Nathan B, Saeed A,
Holme B, Thomas W. Cystic brosis-related di-
abetes: current trends in prevalence, incidence,
and mortality. Diabetes Care 2009;32:1626
1631
52. Moran A, Pekow P, Grover P, et al.; Cystic
Fibrosis Related Diabetes Therapy Study Group.
Insulin therapy to improve BMI in cystic brosis-
related diabetes without fasting hyperglycemia:
results of the Cystic Fibrosis Related Diabetes
Therapy trial. Diabetes Care 2009;32:1783
1788
53. Onady GM, Stol A. Insulin and oral agents
for managing cystic brosis-related diabetes.
Cochrane Database Syst Rev 2013;7:CD004730
54. Moran A, Brunzell C, Cohen RC, et al.; CFRD
Guidelines Committee. Clinical care guidelines
for cystic brosis-related diabetes: a position
statement of the American Diabetes Associa-
tion and a clinical practice guideline of the Cystic
Fibrosis Foundation, endorsed by the Pediatric
Endocrine Society. Diabetes Care 2010;33:
26972708
55. Carpenter MW, Coustan DR. Criteria for
screening tests for gestational diabetes. Am J
Obstet Gynecol 1982;144:768773
56. National Diabetes Data Group. Classica-
tion and diagnosis of diabetes mellitus and
other categories of glucose intolerance. Diabe-
tes 1979;28:10391057